Very high levels of good cholesterol may increase risk of heart attack and death

In continuation of my update on Cholesterol

Very high levels of high-density lipoprotein (HDL or "good") cholesterol may be associated with an increased risk of heart attack and death, according to research presented today at ESC Congress 2018.

Study author Dr Marc Allard-Ratick, of Emory University School of Medicine, Atlanta, US, said: "It may be time to change the way we view HDL cholesterol. Traditionally, physicians have told their patients that the higher your 'good' cholesterol, the better. However, the results from this study and others suggest that this may no longer be the case."

HDL cholesterol has been considered "good" because the HDL molecule is involved in the transport of cholesterol from the blood and blood vessel walls to the liver and ultimately out of the body, thereby reducing the risk of clogged arteries and atherosclerosis. People with low HDL cholesterol have a greater risk of atherosclerosis and cardiovascular disease. But the protective effect of very high HDL cholesterol has been unclear.

This study, conducted as part of the Emory Cardiovascular Biobank, investigated the relationship between HDL cholesterol levels and the risk of heart attack and death in 5,965 individuals, most of whom had heart disease. The average age of participants was 63 years and 35% were female.

Participants were divided into five groups according to their HDL cholesterol level: less than 30 mg/dl (0.78 mmol/L), 31-40 mg/dl (0.8-1 mmol/L); 41-50 mg/dl (1.1-1.3 mmol/L); 51-60 mg/dl (1.3-1.5 mmol/L); and greater than 60 mg/dl (1.5 mmol/L).

During a median follow-up of four years, 769 (13%) participants had a heart attack or died from a cardiovascular cause. Participants with HDL cholesterol 41-60 mg/dl (1.1-1.5 mmol/L) had the lowest risk of heart attack or cardiovascular death. Risk was increased both in participants with low levels (less than 41 mg/dl) and very high levels (greater than 60 mg/dl) of HDL cholesterol, which produced a U-shaped curve when plotted graphically.

Participants with HDL cholesterol levels greater than 60 mg/dl (1.5 mmol/L) had a nearly 50% increased risk of dying from a cardiovascular cause or having a heart attack compared to those with HDL cholesterol levels 41-60 mg/dl (1.1-1.5 mmol/L).

The associations were consistent even after controlling for other risk factors for heart disease such as diabetes, smoking, and low-density lipoprotein (LDL or "bad") cholesterol, as well as other factors linked with high HDL cholesterol such as alcohol intake, race, and sex.

The results support findings from several large population-based studies, including a recent publication which found increased cardiovascular and all-cause death when HDL cholesterol reached extremely high levels. Dr Allard-Ratick said: "Our results are important because they contribute to a steadily growing body of evidence that very high HDL cholesterol levels may not be protective, and because unlike much of the other data available at this time, this study was conducted primarily in patients with established heart disease."

He noted that more research is needed to elucidate the mechanisms of this paradoxical association. "While the answer remains unknown, one possible explanation is that extremely elevated HDL cholesterol may represent 'dysfunctional HDL' which may promote rather than protect against cardiovascular disease," he said.

Dr Allard-Ratick concluded: "One thing is certain: the mantra of HDL cholesterol as the 'good' cholesterol may no longer be the case for everyone."

Ref : https://www.escardio.org/The-ESC/Press-Office/Press-releases/Too-much-of-a-good-thing-Very-high-levels-of-good-cholesterol-may-be-harmful

Entresto drug can be initiated early and safely in heart failure patients with reduced ejection fraction

In continuation of my update on sacubitril/valsartan

Data from the TRANSITION study presented today at the European Society of Cardiology (ESC) Congress in Munich, Germany has shown that Entresto® (sacubitril/valsartan) can be initiated early and safely in a wide range of heart failure patients with reduced ejection fraction (HFrEF) who have been stabilized after hospitalization due to an acute heart failure episode. Patients involved in the study included those with no prior experience of Entresto or conventional HF therapies, as well as those with prior experience of conventional HF therapies.

About half of all heart failure patients have reduced ejection fraction, and optimizing treatment for these patients according to guidelines is critical to reduce the likelihood of another acute episode or dying. However, there is often hesitancy to initiate a new treatment after a hospitalization as these patients are considered 'vulnerable' and unable to tolerate changes in their medication.

"In the weeks following an episode of acute heart failure, patients are very vulnerable and face a high risk of re-hospitalization and death," said Prof. Rolf Wachter, University Hospital Leipzig, Germany and study investigator. "The PARADIGM-HF study showed that sacubitril/valsartan reduces heart failure-related hospitalizations, re-hospitalization and death. TRANSITION shows that sacubitril/valsartan can be initiated early and safely in patients shortly after an acute heart failure episode, providing physicians with added confidence to optimize their care with innovative medicines in heart failure treatment."

In TRANSITION, the safety and tolerability of Entresto were assessed in HFrEF patients after they have been stabilized following an acute heart failure episode. Patients were randomized to initiate Entresto therapy either in the hospital (pre-discharge) or shortly after leaving the hospital (post-discharge). At 10 weeks, more than 86% of patients were receiving Entresto for 2 weeks or longer without interruption and about half of patients in the study achieved the primary endpoint which was a target dose of 200 mg of Entresto twice daily within 10 weeks in both groups. The number of patients who met the primary and secondary endpoints was similar across both treatment arms. The incidence of adverse events and discontinuations of Entresto due to adverse events was also similar in both the in-hospital and the out-patient setting.

"We are encouraged by the findings of TRANSITION which show that Entresto, the new standard of care in heart failure, can be safely initiated in recently hospitalized patients," said Shreeram Aradhye, MD, Chief Medical Officer and Global Head, Medical Affairs, Novartis Pharmaceuticals. "Heart failure is a serious progressive disease with 83% of patients hospitalized at least once for an acute heart failure episode during the course of their condition. Hospitalization provides an opportunity for physicians to optimize heart failure treatment according to guidelines to reduce the likelihood of hospital readmission and death, reduce the burden of hospitalizations, and improve patient outcomes."

Ref : https://www.novartis.com/news/media-releases/novartis-announces-new-data-show-entresto-sacubitrilvalsartan-can-be-initiated-early-safely-hospitalized-patients-after-acute-heart-failure-episode

Food scientists turn soy milk residue into healthy probiotic drink

In continuation of my update on Soy Milk

Food scientists at the National University of Singapore (NUS) have given okara - the residue from the production of soy milk and tofu, and is usually discarded - a new lease of life by turning it into a refreshing drink that contains live probiotics, dietary fiber, free isoflavones and amino acids. By encapsulating these nutrients in a beverage, they can be easily absorbed into the body, and promote gut health.

Created using a patented, zero-waste process, the tasty drink can be stored at room temperature for up to six weeks and still retain high counts of live probiotics to better deliver health effects. This is unlike commercially available probiotic drinks which are mainly dairy-based and require refrigeration to maintain their levels of live probiotics. These beverages also have an average shelf-life of four weeks, and do not contain free isoflavones, which have a host of health benefits.

"Okara has an unpleasant smell and taste - it smells fishy, tastes bland, and has a gritty mouthfeel. Our breakthrough lies in our unique combination of enzymes, probiotics and yeast that work together to make okara less gritty, and give it a fruity aroma while keeping the probiotics alive. Our final product offers a nutritious, non-dairy alternative that is eco-friendly," said project supervisor Associate Professor Shao-Quan Liu, who is from the Food Science and Technology Program at the NUS Faculty of Science.

Turning unwanted soy pulp into a nutritious drink

About 10,000 tonnes of okara are produced yearly in Singapore. As it turns bad easily, causing it to give out an unpleasant smell and a sour taste, okara is usually discarded by soy food producers as food waste.

The idea of using fermentation to produce a drink from okara was first conceived by Ms Weng-Chan Vong, a PhD student from the NUS Food Science and Technology Program. She recounted, "Fermented soy products, such as soybean paste and miso, are common in Asian food culture. When I was young, my grandparents explained to me how these fermented foods are made. The fermentation process was like magic to me - it transforms bland food into something delicious."

"During my undergraduate studies at NUS, I worked on a project to examine how soy milk can be infused into different food items, and I realized that a huge amount of okara was being discarded. It occurred to me that fermentation can be one good way to convert unwanted okara into something that is nutritious and tastes good," she added.

Under the guidance of Assoc Prof Liu, Ms Vong took a year to devise a novel recipe that converts okara into a beverage that is fruity and refreshing. She experimented with 10 different yeasts and four different enzymes before coming up with an ideal combination.

The final recipe uses the probiotic strain Lactobacillus paracasei L26, the Viscozyme ® L enzyme and the Lindnera saturnus NCYC 22 yeast to convert the okara into a nutritious drink that achieves a minimum of 1 billion probiotics per serving, which is the current recommendation by the International Scientific Association for Probiotics and Prebiotics to achieve maximum health benefits. The drink, which takes about one and a half days to produce, also contains free isoflavones, which are naturally occurring antioxidants that maintain cardiovascular health, as well as dietary fiber and amino acids.

Next step: Refining the recipe for commercialization

The NUS researchers have filed a patent for their novel technique, and are currently experimenting with different enzymes and microorganisms to refine their recipe. They are also looking to collaborate with industry partners to introduce the drink to consumers.

"In recent years, the food and beverage industry has been intensifying efforts to develop products that appeal to consumers who are increasingly health conscious. Our new product offers soy food manufacturers a viable solution to reduce waste, and also enables them to provide a healthy and eco-friendly beverage for their customers," said Assoc Prof Liu.

Matcha green tea kills breast cancer stem cells

MATCHA, the Green Tea packed with antioxidants, is often hailed as containing properties which prevent disease.

Scientists in Salford, UK have shed a ray of light on the claim by testing it on cancer stem cells - with surprising results.

In research published in the journal Aging, a team from the Biomedical Research Centre at the University of Salford, used metabolic phenotyping on cell lines of breast cancer stem cells and found that Matcha "shifted cancer cells towards a quiescent metabolic state" and stopped their spread at a relatively low concentration (0.2 mg/ml).

They also found that the signaling pathways that promote cancer stem cells indicated that Matcha "strongly affected mTOR signals, weakening components of the 40S ribosome. This raised the possibility that Matcha could be used in place of chemical drugs such as rapamycin.

Michael Lisanti, professor of translational medicine at the center, explained: "Matcha green tea is a natural product used as a dietary supplement with great potential for a range of treatments. But, the molecular mechanism underpinning all that remains largely unknown.

"By using metabolic phenotyping, we found that the tea is suppressing oxidative mitochondrial metabolism - in other words it is preventing the cells from 're-fuelling' and therefore they become inactive and die.

"The effects on human breast cancer cells were very striking; the active ingredients in matcha having a surgical effect in knocking out certain signaling pathways.

"Our results are consistent with the idea that Matcha may have significant therapeutic potential, mediating the metabolic reprogramming of cancer cells."

The team who specialize in identifying non-toxic methods of killing cancer stem cells recently found that Earl Grey tea ingredient, Bergamot kills cancer cells and works as an anti-cholesterol agent.

Ref : https://www.salford.ac.uk/news/articles/2018/green-tea-prevent-cancer-cells-from-refuelling

Matcha green tea kills breast cancer stem cells

MATCHA, the Green Tea packed with antioxidants, is often hailed as containing properties which prevent disease.

Scientists in Salford, UK have shed a ray of light on the claim by testing it on cancer stem cells - with surprising results.

In research published in the journal Aging, a team from the Biomedical Research Centre at the University of Salford, used metabolic phenotyping on cell lines of breast cancer stem cells and found that Matcha "shifted cancer cells towards a quiescent metabolic state" and stopped their spread at a relatively low concentration (0.2 mg/ml).

They also found that the signaling pathways that promote cancer stem cells indicated that Matcha "strongly affected mTOR signals, weakening components of the 40S ribosome. This raised the possibility that Matcha could be used in place of chemical drugs such as rapamycin.

Michael Lisanti, professor of translational medicine at the center, explained: "Matcha green tea is a natural product used as a dietary supplement with great potential for a range of treatments. But, the molecular mechanism underpinning all that remains largely unknown.

"By using metabolic phenotyping, we found that the tea is suppressing oxidative mitochondrial metabolism - in other words it is preventing the cells from 're-fuelling' and therefore they become inactive and die.

"The effects on human breast cancer cells were very striking; the active ingredients in matcha having a surgical effect in knocking out certain signaling pathways.

"Our results are consistent with the idea that Matcha may have significant therapeutic potential, mediating the metabolic reprogramming of cancer cells."

The team who specialize in identifying non-toxic methods of killing cancer stem cells recently found that Earl Grey tea ingredient, Bergamot kills cancer cells and works as an anti-cholesterol agent.

Ref : https://www.salford.ac.uk/news/articles/2018/green-tea-prevent-cancer-cells-from-refuelling

Kisqali (ribociclib) Approved for Additional Indications in HR+/HER2- Advanced Breast Cancer

In continuation of my update on ribociclib

Novartis  announced a new approval for Kisqali (ribociclib) from the US Food and Drug Administration (FDA) for women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer. Kisqali is now the only CDK4/6 inhibitor indicated for use with an aromatase inhibitor for the treatment of pre-, peri- or postmenopausal women in the US, and also is indicated for use in combination with fulvestrant as both first- or second-line therapy in postmenopausal women[1]. FDA reviewed this supplemental New Drug Application (sNDA) under its Real-Time Oncology Review and Assessment Aid pilot programs and approved the application in less than one month after submission.

"Compelling data for Kisqali have led to the broadest first-line indications of any CDK4/6 inhibitor," said Liz Barrett, CEO, Novartis Oncology. "With this new approval Kisqali has the potential to help even more people in the US live a longer life without progression of disease from this incurable form of breast cancer."

This approval is based on the pivotal MONALEESA-7 and MONALEESA-3 Phase III clinical trials that demonstrated prolonged progression-free survival (PFS) and improvements as early as eight weeks for Kisqali-based regimens compared to endocrine therapy alone[1]. In MONALEESA-7, Kisqali plus an aromatase inhibitor and goserelin nearly doubled the median PFS compared to an aromatase inhibitor and goserelin alone (27.5 months compared to 13.8 months; HR=0.569; 95% CI: 0.436-0.743) in pre- or perimenopausal women[1]. In MONALEESA-3, Kisqali plus fulvestrant demonstrated a median PFS of 20.5 months compared to 12.8 months for fulvestrant alone (HR=0.593; 95% CI: 0.480-0.732) across the overall population of first-line and second-line postmenopausal women[1].

"These MONALEESA clinical trial program data add to the body of evidence that CDK 4/6 inhibition, in the case of these studies with ribociclib, gives women diagnosed with HR+/HER2- advanced breast cancer an important first-line treatment option," said Dennis J. Slamon, MD, Director of Clinical/Translational Research, University of California, Los Angeles Jonsson Comprehensive Cancer Center. "Based on Phase III trial results that consistently showed clinical benefit, physicians should be encouraged to re-evaluate treatment for advanced breast cancer in the first-line setting."

Approximately 155,000 people in the US are living with metastatic breast cancer[2]. Up to one-third of patients with early-stage breast cancer will subsequently develop advanced disease, for which there is currently no cure[3]. Advanced breast cancer in premenopausal women is a biologically distinct and more aggressive disease, and it is the leading cause of cancer death in women 20-59 years old[4],[5].

"Premenopausal women diagnosed with advanced breast cancer often face unique social challenges and a poorer prognosis. For the first time in nearly 20 years, we have results from a dedicated clinical trial among these women," said Jennifer Merschdorf, CEO, Young Survival Coalition. "With this approval, some younger women now have a new therapy indicated specifically for them that may help extend their lives without progression of disease."

FDA Approves Perseris (risperidone) for Extended-Release Injectable Suspension for the Treatment of Schizophrenia in Adults

In continuation of my update on risperidone

Indivior PLC,   announced that the U.S. Food and Drug Administration (FDA) has approved Perseris, the first once-monthly subcutaneous risperidone-containing, long-acting injectable (LAI) for the treatment of schizophrenia in adults. Clinically relevant levels were reached after the first injection of Perseris without use of a loading dose or any supplemental oral risperidone.

"Treatment adherence is a major challenge in schizophrenia due to the complexity of the disease. It is important to have additional treatment options available to physicians to help them improve their patients' symptom severity," said Maurizio Fava, Executive Vice Chair of the Massachusetts General Hospital (MGH) Department of Psychiatry and Indivior clinical research consultant. "The studies carried out by Indivior suggest that Perseris may offer patients, caregivers and physicians a new once-monthly subcutaneous medication option to treat adults with schizophrenia."

Perseris contains risperidone, a well-established treatment for schizophrenia, and uses the extended-release delivery system to form a subcutaneous (under the skin) depot that provides sustained levels of risperidone over one month. Initial peak risperidone plasma levels occur within 4 to 6 hours of dosing and are due to an initial release of the drug during the depot formation process.

"Schizophrenia is a devastating, chronic and often disabling mental health condition that impacts the lives of people suffering from this illness, their families and caregivers. The approval of Perseris brings us the opportunity to provide adult patients and their healthcare providers with an innovative treatment option that we believe will make a meaningful difference," said Shaun Thaxter, Chief Executive Officer of Indivior. "People with schizophrenia face a complex patient journey that can be hindered by ignorance, apathy and stigma. Indivior is committed to working with stakeholders to reduce the stigma of schizophrenia and expand access to evidence-based treatment."

The efficacy of Perseris was evaluated in a pivotal Phase 3 randomized, double-blind, placebo-controlled, 8-week study of 354 patients (NCT 02109562). Perseris efficacy was demonstrated by an improvement in the primary clinical endpoint, Positive and Negative Syndrome Scale (PANSS) total score at day 57. The improvement in Clinical Global Impression Severity of Illness (CGI-S) was also statistically significant at day 57. Clinical trials of Perseris were designed for the product to be initiated with neither a loading dose nor any supplemental risperidone.

The safety of Perseris was evaluated in 814 adults with schizophrenia who received at least one dose of Perseris during clinical trials. A total of 322 patients were treated with Perseris for at least six months, with 234 of those treated with Perseris for at least 12 months. The systemic safety profile of Perseris was consistent with the known safety profile of oral risperidone. The most common systemic adverse reactions in the pivotal Phase 3 trial (in ≥5% of Perseris patients and greater than twice placebo) were increased weight, sedation/somnolence and musculoskeletal pain. The most common injection site reactions (≥5% of all patients across Perseris and placebo groups) were injection site pain and reddening of the skin.

https://www.drugs.com/history/perseris.html

United Therapeutics Announces FDA Approval of the Implantable System for Remodulin

In continuation of my update on treprostinil

United Therapeutics Corporation,  announced approval by the U.S. Food and Drug Administration (FDA) of a New Drug Application (NDA) for the use of Remodulin (treprostinil) Injection in the Implantable System for Remodulin® (ISR).

The ISR has been developed under a collaboration with Medtronic (NYSE: MDT). In December 2017, Medtronic received FDA approval of a premarket application (PMA) for a proprietary intravascular infusion catheter to be used with its SynchroMed™ II implantable infusion pump and related infusion system components (together referred to as the Implantable System for Remodulin) in order to deliver Remodulin for the treatment of pulmonary arterial hypertension (PAH).

"We are extremely excited to offer this new option to patients suffering from PAH," said Martine Rothblatt, Ph.D., Chairman and Chief Executive Officer of United Therapeutics. "During the course of the DelIVery study, we received considerable physician and patient interest in the ISR. We are grateful to our collaborators at Medtronic for reaching this milestone and look forward to continuing our collaboration."

Remodulin was originally approved by the FDA to treat PAH by continuous subcutaneous and intravenous routes of administration in 2002 and 2004, respectively, using external pumps. In the case of intravenous users, the therapy can be very burdensome and brings a risk of sepsis due to the use of a central indwelling catheter.

The ISR provides patients a new option for delivery of intravenous Remodulin, where the entire delivery system is implanted into the body and will be refilled by healthcare professionals at intervals of up to 16 weeks depending on the patient's dose, using a syringe needle through the patient's skin.

"External infusion pumps have been used to deliver prostacyclins for PAH, but managing the therapy places a significant burden on patients, interferes with their daily activities, and runs a high risk of infections," said David Steinhaus, M.D., general manager of the Heart Failure business, part of the Cardiac and Vascular Group at Medtronic. "This fully implantable drug delivery system was designed to address these serious patient care concerns."

United Therapeutics funded and Medtronic conducted the DelIVery for PAH clinical trial, which was a safety study of a new implantable catheter designed for intravascular drug (Remodulin) delivery with the SynchroMed™ II implantable infusion pump. In 2013, the study met its primary objective of demonstrating a rate of catheter-related complications below 2.5 per 1,000 patient-days while using the fully implantable system (p < 0.0001).

https://www.drugs.com/newdrugs/united-therapeutics-announces-fda-approval-implantable-remodulin-4790.html

FDA Approves Mulpleta (lusutrombopag) for Thrombocytopenia in Adults with Chronic Liver Disease

FDA, approved lusutrombopag (Mulpleta, Shionogi Inc.) for thrombocytopenia in adults with chronic liver disease who are scheduled to undergo a medical or dental procedure.

Approval was based on two randomized, double-blind, placebo-controlled trials (L-PLUS 1 and L-PLUS 2, NCT02389621) involving 312 patients with chronic liver disease and severe thrombocytopenia who were undergoing an invasive procedure and had a platelet count less than 50 x 109/L. Patients were randomized 1:1 to receive 3 mg of lusutrombopag or placebo once daily for up to 7 days.

In L-PLUS 1, 78% of patients (38/49) receiving lusutrombopag required no platelet transfusion prior to the primary invasive procedure, compared with 13% (6/48) who received placebo (95% CI for treatment difference: 49%, 79%; p<0.0001). In L-PLUS 2, 65% (70/108) of patients who received lusutrombopag required no platelet transfusion prior to the primary invasive procedure or rescue therapy for bleeding from randomization through 7 days after the procedure, compared with 29% (31/107) receiving placebo (95% CI for treatment difference: 25%, 49%; p<0.0001).

The most common adverse reaction in ≥ 3% of patients was headache.

The recommended lusutrombopag dosage is 3 mg orally once daily with or without food for 7 days.

FDA granted this application priority review and fast track designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Ref : https://en.wikipedia.org/wiki/Lusutrombopag

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FDA Approves Mulpleta (lusutrombopag) for Thrombocytopenia in Adults with Chronic Liver Disease

FDA Approves Orilissa (elagolix) for the Management of Moderate to Severe Pain Associated with Endometriosis

In continuation of my update on elagolix

AbbVie a research-based global biopharmaceutical company, in cooperation with Neurocrine Biosciences, Inc. , announced that the U.S. Food and Drug Administration (FDA) approved Orilissa (elagolix), the first and only oral gonadotropin-releasing hormone (GnRH) antagonist specifically developed for women with moderate to severe endometriosis pain. The FDA approved Orilissa under priority review. Orilissa represents the first FDA-approved oral treatment for the management of moderate to severe pain associated with endometriosis in over a decade and is expected to be available in U.S. retail pharmacies in early August 2018.

"Orilissa represents a significant advancement for women with endometriosis and physicians who need more options for the medical management of this disease," said Michael Severino, M.D., Executive Vice President, Research and Development and Chief Scientific Officer, AbbVie. "The approval of Orilissa demonstrates AbbVie's continued commitment to address serious diseases and unmet needs."

Endometriosis is one of the most common gynecologic disorders in the U.S.3 It affects an estimated one in 10 women of reproductive age and can be associated with pain symptoms that can be debilitating.3,4 Women can suffer for up to six to 10 years and visit multiple physicians before receiving a proper diagnosis.5,6

Endometriosis-associated pain is often managed with medicines such as oral contraceptives, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids and hormonal therapies, which can work for some women but very few are specifically indicated for the treatment of endometriosis.3,7 In more extensive cases, surgical interventions (e.g., laparotomy, laparoscopy or hysterectomy) are often pursued, and may not be curative for all individuals.8

"Endometriosis is often characterized by chronic pelvic pain that can impact women's daily activities," said Hugh S. Taylor, M.D., study investigator and Chair of the Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine. "Women with endometriosis may undergo multiple medical treatments and surgical procedures seeking pain relief and this approval gives physicians another option for treatment based on a woman's specific type and severity of endometriosis pain."

The approval is supported by data from two replicate studies in the largest endometriosis Phase 3 study program conducted to date, which evaluated nearly 1,700 women with moderate to severe endometriosis pain. Clinical trial data demonstrated Orilissa significantly reduced the three most common types of endometriosis pain: daily menstrual pelvic pain, non-menstrual pelvic pain and pain with sex. A higher proportion of women treated with Orilissa 150 mg once daily and 200 mg twice daily were responders for daily menstrual pain and non-menstrual pelvic pain compared to placebo in a dose-dependent manner at month three. Women were defined as responders if they experienced a reduction in daily menstrual pain and non-menstrual pelvic pain with no increase in analgesic use (nonsteroidal anti-inflammatory drug or opioid) for endometriosis-associated pain.

Both Orilissa treatment groups showed statistically significant greater mean decreases from baseline compared to placebo in daily menstrual pain and non-menstrual pelvic pain at month six. Women in the Phase 3 studies also provided a daily self-assessment of their endometriosis pain using a numeric rating scale (NRS) and women taking Orilissa 150 mg once daily and 200 mg twice daily reported a statistically (p <0.001) significant reduction from baseline in NRS scores compared to placebo at month three. Clinical trial data also demonstrated women taking Orilissa 200 mg twice daily showed statistically significant greater reduction in pain with sex from baseline to month three compared to placebo.

The recommended duration of use for Orilissa is up to 24 months for the 150 mg once daily dose and up to six months for the 200 mg twice daily dose, as it causes a dose-dependent decrease in bone mineral density (BMD). BMD loss is greater with increasing duration of use and may not be completely reversible after stopping treatment. For women with moderate hepatic impairment, the recommended dosage is 150 mg once daily for up to six months. Orilissa is recommended to be taken orally at approximately the same time each day, with or without food.

"Together with AbbVie, we are proud to offer a treatment option for the many women suffering from pain associated with endometriosis," said Kevin Gorman, Ph.D., Chief Executive Officer of Neurocrine Biosciences. "Neurocrine discovered Orilissa nearly twenty years ago and through our partnership with AbbVie, the approval of Orilissa reflects our joint commitment to develop therapies for difficult to manage conditions in underserved patient populations."

Ref : https://en.wikipedia.org/wiki/Elagolix

FDA Approves Orilissa (elagolix) for the Management of Moderate to Severe Pain Associated with Endometriosis